PROJECT SUMMARY This research program aims to elucidate the role of the ipsilateral hemisphere in motor control, entailing parallel studies of upper limb movement in monkey and human. The outcome of the proposed work has the potential to guide the development of cortically-controlled neuroprosthetic systems for patients with neurological disorders by recording from humans and monkeys at different spatial levels of functional neural organization. Previous work from our group has demonstrated that distributed activity in primate motor areas is reliably correlated with ipsilateral upper limb kinematics in monkey and human. This information can be decoded by applying linear methods to neural signals at a variety of temporal and spatial scales, and can be successfully incorporated into a closed-loop BMI system. However, the functional contribution of ipsilateral motor cortex to limb movement remains unclear. Is ipsilateral control limited to proximal muscles or are these signals also relevant for the control of distal muscles? How do ipsilateral representations change in different task contexts, especially when considering contexts in which the two hands are either used independently or in a coordinated manner? This research program will address these fundamental questions. We outline four key hypotheses: H1) Activity in motor cortex provides additional control signals for ipsilateral movements, independent of the activity dedicated to contralateral movements. H2) Movements of one limb transcallosally activate homologous circuits in the ipsilateral motor cortex, activity that might facilitate mirror-symmetric movement or provide a mechanism for generalized motor learning. H3) Activity in ipsilateral motor cortex reflects the simultaneous, bilateral preparation of unimanual movements. H4) Ipsilateral motor activity is related to the control of the contralateral hand, but is modulated by the degree of ipsilateral movements as part of a network required for bimanual coordination. To evaluate these hypotheses, this proposal is structured around two aims, each entailing a series of experiments. The specific aims in both monkey and man are: 1) to characterize the role of ipsilateral motor cortex during unimanual movement and 2) to characterize the role of ipsilateral motor cortex during bimanual movements. Parallel neurophysiological studies will be conducted in human and non-human primates to record and analyze neural activity at different levels of integration. State-of- the-art methods for complementary neural recordings (human electrocorticogram, monkey local field potential and single unit activity) and data analysis will be employed to address the four hypotheses.